Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction.
OBJECTIVE
Blockade of bradykinin breakdown and enhancement of prostaglandin release probably participate in the antihypertensive activity of angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase blockers may attenuate the efficacy of ACE inhibitors by interfering with prostaglandin synthesis, and patients taking aspirin may not benefit from ACE inhibition. This study was designed to evaluate the incidence of the counteractive phenomenon and to define minimal aspirin dosage that causes an antagonistic effect.


METHODS
These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe untreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in group 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenuation of more than 20% of the mean blood pressure decrease produced by enalapril was the criteria that defined antagonism.


RESULTS
The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: mean arterial pressure was lowered by 63% and 91% less, respectively. Results were independent of the drug administration order. In "responders," aspirin significantly attenuated the renin rise associated with ACE inhibition.


CONCLUSIONS
These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardless of hypertension severity. Antagonism may be mediated through prostaglandin inhibition according to predominance, in an individual patient, of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.
Guazzi
M D
MD
Istituto di Cardiologia dell'Università degli Studi, Centro di Studio per le Ricerche Cardiovascolari del CNR, Fondazione Monzino, IRCCS, Milano, Italy.
Campodonico
J
J
Celeste
F
F
Guazzi
M
M
Santambrogio
G
G
Rossi
M
M
Trabattoni
D
D
Alimento
M
M
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004334:Drug Administration Schedule; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D012720:Severity of Illness Index
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D004656:Enalapril; D001241:Aspirin